A 4arm-PEG macromolecule crosslinked chitosan hydrogels as antibacterial wound dressing.

In order to develop better wound dressings, a novel chitosan hydrogel (Cn-Nm gel) was designed and fabricated by using aldehyde-4-arm polyethylene glycol (4r-PEG-CHO) to crosslink the chitosan dissolved in alkaline solution, amino-4-arm polyethylene glycol (4r-PEG-NH2) was chosen as the additive simultaneously. The special dissolution technique and macromolecular crosslinking structure endows the Cn-Nm gels with better performance than that of gels prepared by acid dissolving method with micromolecule crosslinker. First, Cn-Nm gels own strong toughness with 500 kPa tensile strength and 1000% elongation, about 400% swelling ratio and fast water absorption rate. Second, about 300 kPa adhesive strength and strippability between the gels and skin is achieved. More importantly, Cn-Nm gels show nearly 100% antibacterial rate towards Escherichia coli and Staphylococcus aureus. Excellent biocompatibility is also proved by the mouse fibroblasts tests. All of the performance makes this developed chitosan-based gel be the potential candidate as a wound dressing.

Systemic delivery of siRNA to the colon using peptide modified PEG-PCL polymer micelles for the treatment of ulcerative colitis.

Ulcerative colitis (UC) is a refractory inflammatory bowel disease that causes inflammation and ulcers in the digestive tract, and significantly reduces the patient's quality of life. While existing UC treatments have many challenges, nanotechnology, and small interfering RNA (siRNA) based formulations are novel and promising for UC treatment. We previously reported that intravenous administration of MPEG-PCL-CH2R4H2C nanomicelles had high inflammatory site accumulation and remarkable therapeutic effects on rheumatoid arthritis by a phenomenon similar to enhanced permeability and retention effect. In this study, we investigated the effects of siRNA delivered using MPEG-PCL-CH2R4H2C nanomicelles through intravenous administration to the inflammation site of dextran sulfate sodium-induced colitis mice. The MPEG-PCL-CH2R4H2C micelles had optimum physical properties and high siRNA compaction ability. Moreover, model-siRNA delivered through MPEG-PCL-CH2R4H2C showed higher accumulation in the inflammatory site than that of the naked siRNA. Furthermore, intravenous administration of MPEG-PCL-CH2R4H2C/siRelA micelles, targeting siRelA, a subunit of NF-κB, significantly decreased the shortening of large intestine, clinical score, and production of inflammatory cytokines compared the 5-ASA and naked siRelA. These results suggest that MPEG-PCL-CH2R4H2C is a useful carrier for the systemic delivery and accumulation of siRNA, thus improving its therapeutic effect.

Stable Loading and Delivery of Melittin with Lipid-Coated Polymeric Nanoparticles for Effective Tumor Therapy with Negligible Systemic Toxicity.

Melittin is a potential anticancer candidate with remarkable antitumor activity and ability to overcome tumor drug resistance. However, the clinical applications of melittin are largely restricted by its severe hemolytic activity and nonspecific cytotoxicity after systemic administration. Here, a biocompatible and stable melittin-loaded lipid-coated polymeric nanoparticle (MpG@LPN) formulation that contains a melittin/poly-γ-glutamic acid nanoparticle inner core, a lipid membrane middle layer, and a polyethylene glycol (PEG) and PEG-targeting molecule outer shell was designed. The formulations were prepared by applying a self-assembly procedure based on intermolecular interactions, including electrostatic attraction and hydrophobic effect. The core-shell MpG@LPN presented high efficiency for melittin encapsulation and high stability in physiological conditions. Hemolysis and cell proliferation assays showed that the PEG-modified MpG@LPN had almost no hemolytic activity and nonspecific cytotoxicity even at high concentrations. The modification of targeting molecules on the MpG@LPNs allowed for the selective binding with target tumor cells and cytolytic activity via apoptosis induction. In vivo experiments revealed that MpG@LPNs can remarkably inhibit the growth of tumors without the occurrence of hemolysis and tissue toxicity. Results suggested that the developed MpG@LPN with a core-shell structure can effectively address the main obstacles of melittin in clinical applications and has great potential in cancer treatment.

Super-fast in situ formation of hydrogels based on multi-arm functional polyethylene glycols as endotamponade substitutes.

Polymer-based hydrogels used in the vitreous cavity could lead to an unsatisfactory gel-forming state, uncontrollable swelling, and potential cytotoxicity. Their application can significantly impair the filling effect and cause severe side effects in the surrounding tissues. To address the concerns, a poly(ethylene glycol)-engineered hydrogel capable of fast in situ gel formation (less than 1 min), with an ultralow swelling ratio and no cytotoxicity in the rabbits' eyes, was constructed as a vitreous substitute. The multi-arm polyethylene glycols (PEGs) modified with functional groups (thiol and maleimide) possess high reaction efficiency in the vitreous cavity and present excellent biomimetic characteristics of the natural vitreous humor in vitro. After injection with a double syringe via a 25-gauge needle in the eyes of rabbits for 6 months, the hydrogel functioned as an artificial vitreous body that could highly promote retinal detachment repair, with excellent biocompatibility and high transparency, and without bio-degradation or ocular complications. Collectively, the fast in situ forming hydrogel could achieve quick and good filling in the vitreous cavity without cytotoxicity, which makes it a promising long-term endotamponade substitute.

Kinetic stability modulation of polymeric nanoparticles for enhanced detection of influenza virus via penetration of viral fusion peptides.

Specific interactions between viruses and host cells provide essential insights into material science-based strategies to combat emerging viral diseases. pH-triggered viral fusion is ubiquitous to multiple viral families and is important for understanding the viral infection cycle. Inspired by this process, virus detection has been achieved using nanomaterials with host-mimetic membranes, enabling interactions with amphiphilic hemagglutinin fusion peptides of viruses. Most research has been on designing functional nanoparticles with fusogenic capability for virus detection, and there has been little exploitation of the kinetic stability to alter the ability of nanoparticles to interact with viral membranes and improve their sensing performance. In this study, a homogeneous fluorescent assay using self-assembled polymeric nanoparticles (PNPs) with tunable responsiveness to external stimuli is developed for rapid and straightforward detection of an activated influenza A virus. Dissociation of PNPs induced by virus insertion can be readily controlled by varying the fraction of hydrophilic segments in copolymers constituting PNPs, giving rise to fluorescence signals within 30 min and detection of various influenza viruses, including H9N2, CA04(H1N1), H4N6, and H6N8. Therefore, the designs demonstrated in this study propose underlying approaches for utilizing engineered PNPs through modulation of their kinetic stability for direct and sensitive identification of infectious viruses.

Elucidation of Distinct Modular Assemblies of Smoothened Receptor by Bitopic Ligand Measurement.

Class F G protein-coupled receptors are characterized by a large extracellular domain (ECD) in addition to the common transmembrane domain (TMD) with seven α-helixes. For smoothened receptor (SMO), structural studies revealed dissected ECD and TMD, and their integrated assemblies. However, distinct assemblies were reported under different circumstances. Using an unbiased approach based on four series of cross-conjugated bitopic ligands, we explore the relationship between the active status and receptor assembly. Different activity dependency on the linker length for these bitopic ligands corroborates the various occurrences of SMO assembly. These results reveal a rigid "near" assembly for active SMO, which is in contrast to previous results. Conversely, inactive SMO adopts a free ECD, which would be remotely captured at "far" assembly by cholesterol. Altogether, we propose a mechanism of cholesterol flow-caused SMO activation involving an erection of ECD from far to near assembly.

Drug development of lyso-thermosensitive liposomal doxorubicin: Combining hyperthermia and thermosensitive drug delivery.

We review the drug development of lyso-thermosensitive liposomal doxorubicin (LTLD) which is the first heat-activated formulation of a liposomal drug carrier to be utilized in human clinical trials. This class of compounds is designed to carry a payload of a cytotoxic agent and adequately circulate in order to accumulate at a tumor that is being heated. At the target the carrier is activated by heat and releases its contents at high concentrations. We summarize the preclinical and clinical experience of LTLD including its successes and challenges in the development process.

Bottlebrush Polymer-Conjugated Melittin Exhibits Enhanced Antitumor Activity and Better Safety Profile.

Despite potency against a variety of cancers in preclinical systems, melittin (MEL), a major peptide in bee venom, exhibits non-specific toxicity, severe hemolytic activity, and poor pharmacological properties. Therefore, its advancement in the clinical translation system has been limited to early-stage trials. Herein, we report a biohybrid involving a bottlebrush-architectured poly(ethylene glycol) (PEG) and MEL. Termed pacMEL, the conjugate consists of a high-density PEG arrangement, which provides MEL with steric inhibition against protein access, while the high molecular weight of pacMEL substantially enhances plasma pharmacokinetics with a ∼10-fold increase in the area under the curve (AUC∞) compared to free MEL. pacMEL also significantly reduces hepatic damage and unwanted innate immune response and all but eliminated hemolytic activities of MEL. Importantly, pacMEL passively accumulates at subcutaneously inoculated tumor sites and exhibits stronger tumor-suppressive activity than molecular MEL. Collectively, pacMEL makes MEL a safer and more appealing drug candidate.

A chitosan hydrogel sealant with self-contractile characteristic: From rapid and long-term hemorrhage control to wound closure and repair.

Emergent and long-term hemorrhage control is requisite and beneficial for reducing global mortality and postoperative complications (e.g., second bleeding and adverse tissue adhesion). Despite recent advance in injectable hydrogels for hemostasis, achieving rapid gelation, strong tissue-adhesive property and stable mechanical strength under fluid physiological environment is still challenging. Herein, we developed a novel chitosan hydrogel (CCS@gel) via dynamic Schiff base reaction and mussel-inspired catechol chemistry. The hydrogel possessed high gelation rate (<10 s), strong wet adhesiveness, excellent self-healing performance and biocompatibility. More importantly, the CCS@gel exhibited saline-induced contractile performance and mechanical enhancement, promoting its mechanical property in moist internal conditions. In vivo studies demonstrated its superior hemostatic efficacy for diverse anticoagulated visceral and carotid bleeding scenarios, compared to commercialized fibrin glue. The hydrogel-treated rats survived for 8 weeks with minimal inflammation and postoperative adhesion. These results revealed that the promising CCS@gel would be a facile, efficient and safe sealant for clinical hemorrhage control.

Generation and Characterization of a Library of Novel Biologically Active Functional Surfactants (Surfmers) Using Combined High-Throughput Methods.

We report the first successful combination of three distinct high-throughput techniques to deliver the accelerated design, synthesis, and property screening of a library of novel, bio-instructive, polymeric, comb-graft surfactants. These three-dimensional, surface-active materials were successfully used to control the surface properties of particles by forming a unimolecular deep layer on the surface of the particles via microfluidic processing. This strategy deliberately utilizes the surfactant to both create the stable particles and deliver a desired cell-instructive behavior. Therefore, these specifically designed, highly functional surfactants are critical to promoting a desired cell response. This library contained surfactants constructed from 20 molecularly distinct (meth)acrylic monomers, which had been pre-identified by HT screening to exhibit specific, varied, and desirable bacterial biofilm inhibitory responses. The surfactant's self-assembly properties in water were assessed by developing a novel, fully automated, HT method to determine the critical aggregation concentration. These values were used as the input data to a computational-based evaluation of the key molecular descriptors that dictated aggregation behavior. Thus, this combination of HT techniques facilitated the rapid design, generation, and evaluation of further novel, highly functional, cell-instructive surfaces by application of designed surfactants possessing complex molecular architectures.

Journey of Poly(ethylene Glycol) in Living Cells.

As the gold standard for stealth polymer materials, poly(ethylene glycol) (PEG) has been widely used in drug delivery with excellent properties such as low toxicity, reduced immunogenicity, good water solubility, and so forth. However, lack of understanding for the fate of PEG and PEGylated delivery systems at the cellular level has limited the application of PEGylated molecules in diagnosis and therapy. Here, we chose linear PEG 5k as a representative model and focused on the internalization behavior and mechanism, intracellular trafficking, sub-cellular localization, and cellular exocytosis of PEG and PEGylated molecules in living cells. Our investigation showed that PEG could be internalized into cells in 1 h. The internalized PEG was localized to lysosome, cytosol, endoplasmic reticulum (ER) and mitochondria. Importantly, the fate of PEG in cells could be regulated by conjugating different small molecules. PEGylated rhodamine B (PEG-RB) as the positively charged macromolecule was internalized into cells by micropinocytosis and then transported in lysosomes, ER, and mitochondria via vesicles sequentially. In contrast, PEGylated pyropheophorbide-a (PEG-PPa) as the negatively charged macromolecule was internalized into cells and transported to lysosomes ultimately. PEGylation slowed down the exocytosis process of RB and PPa and significantly prolonged their residence time inside the cells. These findings improve the understanding of how PEG and PEGylated molecules interact with the biological system at cellular and sub-cellular levels, which is of significance to rational PEGylation design for drug delivery.

Gingipain-Responsive Thermosensitive Hydrogel Loaded with SDF-1 Facilitates In Situ Periodontal Tissue Regeneration.

Existing local drug delivery systems for periodontitis suffer from poor antibacterial effect and unsatisfied periodontal regeneration. In this study, a smart gingipain-responsive hydrogel (PEGPD@SDF-1) was synthesized as an environmentally sensitive carrier for on-demand drug delivery. The PEGPD@SDF-1 hydrogel was synthesized from polyethylene glycol diacrylate (PEG-DA) based scaffolds, dithiothreitol (DTT), and a novel designed functional peptide module (FPM) via Michael-type addition reaction, and the hydrogel was further loaded with stromal cell derived factor-1 (SDF-1). The FPM exhibiting a structure of anchor peptide-short antimicrobial peptide (SAMP)-anchor peptide could be cleaved by gingipain specifically, and the SAMP was released out of the hydrogel for antibacterial effect in response to gingipain. The hydrogel properties were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), swelling ratio analysis, degradation evaluation, and release curve description of the SAMP and SDF-1. Results in vitro indicated the PEGPD@SDF-1 hydrogel exhibited preferable biocompatibility and could promote the proliferation, migration, and osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Antibacterial testing demonstrated that the PEGPD@SDF-1 hydrogel released the SAMP stressfully in response to gingipain stimulation, thereby strongly inhibiting the growth of Porphyromonas gingivalis. Furthermore, the study in vivo indicated that the PEGPD@SDF-1 hydrogel inhibited P. gingivalis reproduction, created a low-inflammatory environment, facilitated the recruitment of CD90+/CD34- stromal cells, and induced osteogenesis. Taken together, these results suggest that the gingipain-responsive PEGPD@SDF-1 hydrogel could facilitate in situ periodontal tissue regeneration and is a promising candidate for the on-demand local drug delivery system for periodontitis.

Singlet Oxygen-Responsive Polymeric Nanomedicine for Light-Controlled Drug Release and Image-Guided Photodynamic-Chemo Combination Therapy.

Coencapsulation of chemotherapeutic agents and photosensitizers into nanocarriers can help to achieve a combination of chemotherapy and photodynamic therapy for superior antitumor effects. However, precise on-demand drug release remains a major challenge. In addition, the loaded photosensitizers usually tend to aggregate, which can significantly weaken their fluorescent signals and photodynamic activities. To address these issues, herein, a smart nanocarrier termed as singlet oxygen-responsive nanoparticle (SOR-NP) was constructed by introducing singlet oxygen (1O2)-sensitive aminoacrylate linkers into amphiphilic mPEG-b-PCL copolymers. Boron dipyrromethene (BDP) and paclitaxel (PTX) as model therapeutic agents were coloaded into an 1O2-responsive nanocarrier for realizing light-controlled drug release and combination cancer treatment. This polymeric nanocarrier could substantially relieve the aggregation of encapsulated BDP due to the presence of a long hydrophobic chain. Therefore, the formed SOR-NPBDP/PTX nanodrug could generate bright fluorescent signals and high levels of 1O2, which could mediate cell death via PDT and rupture aminoacrylate linker simultaneously, leading to collapse of SOR-NPBDP/PTX and subsequent PTX release. The light-triggered drug release and combined anticancer effects of SOR-NPBDP/PTX were validated in HepG2 and MCF-7 cancer cells and H22 tumor-bearing mice. This study provides a promising strategy for tumor-specific drug release and selective photodynamic-chemo combination treatment.

PEGylation of the Antimicrobial Peptide PG-1: A Link between Propensity for Nanostructuring and Capacity of the Antitrypsin Hydrolytic Ability.

The increasing prevalence of antibacterial resistance globally underscores the urgent need for updated antimicrobial peptides (AMPs). Here, we describe a strategy for inducing the self-assembly of protegrin-1 (PG-1) into nanostructured antimicrobial agents with significantly improved pharmacological properties. Our strategy involves PEGylation in the terminals of PG-1 and subsequent self-assembly in aqueous media in the absence of exogenous excipients. Compared with the parent PG-1, the therapeutic index (TI) of NPG750(TIGram-negative bacteria = 17.07) and CPG2000(TIAll = 26.02) was increased. Importantly, NPG750 and CPG2000 offered higher stability toward trypsin degradation. Mechanistically, NPG750 and CPG2000 exerted their bactericidal activity by membrane-active mechanisms due to which microbes were not prone to develop resistance. Our findings proved PEGylation as a simple yet versatile strategy for generating AMP-derived bioactive drugs with excellent antitrypsin hydrolytic ability and lower cytotoxicity. This provides a theoretical basis for the further clinical application of AMPs.

Efficient Design to Monitor the Site-specific Sustained Release of a Non-Emissive Anticancer Drug.

A pH-responsive smart nanocarrier with significant components was synthesized by conjugating the non-emissive anticancer drug methyl orange and polyethylene glycol derived folate moiety to the backbone of polynorbornene. Complete synthesis procedure and characterization methods of three monomers included in the work: norbornene-derived Chlorambucil (Monomer 1), norbornene grafted with polyethylene glycol, and folic acid (Monomer 2) and norbornene attached methyl orange (Monomer 3) connected to the norbornene backbone through ester linkage were clearly discussed. Finally, the random copolymer CHO PEG FOL METH was synthesized by ring-opening metathesis polymerization (ROMP) using Grubbs' second-generation catalyst. Advanced polymer chromatography (APC) was used to find the final polymer's molecular weight and polydispersity index (PDI). Dynamic light scattering, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) were utilized to explore the prodrug's size and morphology. Release experiments of the anticancer drug, Chlorambucil and the coloring agent, methyl orange, were performed at different pH and time. Cell viability assay was carried out for determining the rate of survived cells, followed by the treatment of our final polymer named CHO PEG FOL METH.

Design and In Vitro Evaluation of a Slow-Release Intraocular Implant of Betamethasone.

Posterior eye diseases are a common cause of vision problems in developing countries, which have encouraged the development of new treatment models for these degenerative diseases. Intraocular implants are one of the drug delivery systems to the posterior region of the eye. Using these implants, the blood-eye barrier can be bypassed; the complications caused by repeated in vitro administrations can be eliminated, and smaller amounts of the drug would be used during the treatment process. Meanwhile, biodegradable implants have received more attention due to their biodegradable structure and the lack of need for re-surgery to remove the rest of the system from the eye. The aim of this study is to employ biodegradable implants composed of polyethylene glycol (PEG) and 3-hydroxybutyrate-co-3-hydroxyvalerat (PHBV) to deliver betamethasone to the back of the eye in the treatment of retinopathy. PHBV polymer has been selected as the main polymer with a certain ratio of drug to polymer for fabrication of enamel and different amounts of PEG with three molecular weights used as pore generators to control drug release over a period of time. Based on the analysis of the results of differential scanning calorimetry (DSC) and FTIR spectroscopy, none of the polymers were degraded in the temperature range of the manufacturing process, and among betamethasone derivatives, the best option for implant preparation is the use of its basic form. Drug release studies over a period of three months showed that implants containing PHBV HV2% and PEG 6000 had a more appropriate release profile.

Development of Gelucire® 48/16 and TPGS Mixed Micelles and Its Pellet Formulation by Extrusion Spheronization Technique for Dissolution Rate Enhancement of Curcumin.

The oral bioavailability of curcumin is limited, attributed to its low solubility or dissolution and poor absorption. Herein, the study describes formulation of curcumin-loaded mixed micelles of Gelucire® 48/16 and TPGS for its dissolution rate enhancement. Curcumin was dispersed in these molten lipidic surfactants which was then adsorbed on carrier and formulated as pellets by extrusion spheronization. Critical micelle concentration (CMC) of binary mixture of Gelucire® 48/16 and TPGS was lower than their individual CMC demonstrating the synergistic behavior of mixture. Thermodynamic parameters like partition coefficient and Gibbs free energy of solubilization indicated that mixed micelles were more efficient than micelles of its individual components in curcumin solubilization. Dynamic light scattering (DLS) suggested slight increase in micellar size of mixed micelles than its components suggesting curcumin loading in mixed micelles. Fourier transform infrared spectroscopy (FTIR) revealed that phenolic hydroxyl group interacts with lipids which contribute to its enhanced solubility. Furthermore, the differential scanning calorimetry (DSC) and X-ray diffraction (XRD) study indicated the conversion of crystalline curcumin into amorphous form. In the pellet formulation, Gelucire® 48/16 acted as a binder and eliminated the requirement of additional binder. Microcrystalline cellulose (MCC) forms wet mass and retards the release of curcumin from pellets. Increase in concentration of water-soluble diluent increased drug release. The optimized formulation released more than 90% drug and maintains supersaturation level of curcumin for 2 h. Thus, mixed micellar system was effective delivery system for curcumin while pellet formulation is an interesting formulation strategy consisting semi-solid lipids.

Formulation and In Vitro Characterization of PLGA/PLGA-PEG Nanoparticles Loaded with Murine Granulocyte-Macrophage Colony-Stimulating Factor.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has demonstrated notable clinical activity in cancer immunotherapy, but it is limited by systemic toxicities, poor bioavailability, rapid clearance, and instability in vivo. Nanoparticles (NPs) may overcome these limitations and provide a mechanism for passive targeting of tumors. This study aimed to develop GM-CSF-loaded PLGA/PLGA-PEG NPs and evaluate them in vitro as a potential candidate for in vivo administration. NPs were created by a phase-separation technique that did not require toxic/protein-denaturing solvents or harsh agitation techniques and encapsulated GM-CSF in a more stable precipitated form. NP sizes were within 200 nm for enhanced permeability and retention (EPR) effect with negative zeta potentials, spherical morphology, and high entrapment efficiencies. The optimal formulation was identified by sustained release of approximately 70% of loaded GM-CSF over 24 h, alongside an average size of 143 ± 35 nm and entrapment efficiency of 84 ± 5%. These NPs were successfully freeze-dried in 5% (w/v) hydroxypropyl-ß-cyclodextrin for long-term storage and further characterized. Bioactivity of released GM-CSF was determined by observing GM-CSF receptor activation on murine monocytes and remained fully intact. NPs were not cytotoxic to murine bone marrow-derived macrophages (BMDMs) at concentrations up to 1 mg/mL as determined by MTT and trypan blue exclusion assays. Lastly, NP components generated no significant transcription of inflammation-regulating genes from BMDMs compared to IFNγ+LPS "M1" controls. This report lays the preliminary groundwork to validate in vivo studies with GM-CSF-loaded PLGA/PEG-PLGA NPs for tumor immunomodulation. Overall, these data suggest that in vivo delivery will be well tolerated.

Biodegradable Polymersomes with Structure Inherent Fluorescence and Targeting Capacity for Enhanced Photo-Dynamic Therapy.

Biodegradable nanostructures displaying aggregation-induced emission (AIE) are desirable from a biomedical point of view, due to the advantageous features of loading capacity, emission brightness, and fluorescence stability. Herein, biodegradable polymers comprising poly (ethylene glycol)-block-poly(caprolactone-gradient-trimethylene carbonate) (PEG-P(CLgTMC)), with tetraphenylethylene pyridinium-TMC (PAIE) side chains have been developed, which self-assembled into well-defined polymersomes. The resultant AIEgenic polymersomes are intrinsically fluorescent delivery vehicles. The presence of the pyridinium moiety endows the polymersomes with mitochondrial targeting ability, which improves the efficiency of co-encapsulated photosensitizers and improves therapeutic index against cancer cells both in vitro and in vivo. This contribution showcases the ability to engineer AIEgenic polymersomes with structure inherent fluorescence and targeting capacity for enhanced photodynamic therapy.

Surface modification by poly(ethylene glycol) with different end-grafted groups: Experimental and theoretical study.

Dihydroxyphenylalanine (DOPA) is extensively reported to be a surface-independent anchor molecule in bioadhesive surface modification and antifouling biomaterial fabrication. However, the mechanisms of DOPA adsorption on versatile substrates and the comparison between experimental results and theoretical results are less addressed. We report the adsorption of DOPA anchored monomethoxy poly(ethylene glycol) (DOPA-mPEG) on substrates and surface wettability as well as antifouling property in comparison with thiol and hydroxyl anchored mPEG (mPEG-SH and mPEG-OH). Gold and hydroxylated silicon were used as model substrates to study the adsorptions of mPEGs. The experimental results showed that the DOPA-mPEG showed higher affinity to both gold and silicon wafers, and the DOPA-mPEG modified surfaces had higher resistance to protein adsorption than those of mPEG-SH and mPEG-OH. It is revealed that the surface wettability is primary for surface fouling, while polymer flexibility is the secondary parameter. We present ab initio calculations of the adsorption of mEGs with different end-functionalities on Au and hydroxylated silicon wafer (Si-OH), where the binding energies are obtained. It is established that monomethoxy ethylene glycol (mEG) with DOPA terminal DOPA-mEG is clearly favored for the adsorption with both gold and Si-OH surfaces due to the bidentate Au-O interactions and the bidentate O-H bond interactions, in agreement with experimental evidence.